Project Summary/Abstract Anterior cruciate ligament (ACL) injury is a common activity-related knee injury with a substantial negative impact on individuals and society. Annual direct costs exceed $13 billion, and the long-term indirect costs far exceed that figure, as ACL injury is also linked to the accelerated development of disabling osteoarthritis within a few years after injury. The National Public Health Agenda for Osteoarthritis recommends expanding and enhancing evidence-based ACL injury prevention to reduce this burden. We have identified modifiable movement patterns that increase ACL injury risk in young female athletes. While neuromuscular training targets those injury risk movement patterns and shows statistical efficacy in high-risk athletes, a meaningful transfer of low-risk mechanics to the field of play has been limited. This inability of current approaches to ensure injury-resistant movement pattern transfer to sport is readily apparent as there has not been a decrease in national ACL injury rates in young female athlete despite efficacy of standard neuromuscular training to modify biomechanics in the lab. The key knowledge gap to ensure effective injury prevention transfer to sport is understanding the mechanisms the nervous system engages to acquire and transfer injury-resistant movement patterns from the intervention or laboratory to the athletic field. Thus, the overall objective of this proposal is to determine the neural mechanisms underpinning the transfer of injury-resistant movement patterns to realistic sport scenarios. Our published and recent preliminary data on the neuroplasticity related to injury risk and following neuromuscular training demonstrate a specific neural mechanism underlies the transfer of injury-resistant movement patterns. These preliminary data support this proposal's central hypothesis that changes in brain activity underlie the acquisition and transfer of injury-resistant movement patterns to realistic sport scenarios. Importantly this work indicates the neuroplasticity can be targeted by augmented biofeedback and other clinical methods to optimize brain activation patterns for movement that promote injury-resistant movement pattern acquisition and transfer. The ability to target the neural mechanisms of injury risk factor reduction could revolutionize ACL injury prevention strategies. Once the objectives of this application are achieved, we will be able to enhance the efficacy of neuromuscular training with the identified neuro-therapeutic targets. This contribution will be significant to improve ACL injury prevention training transferability to reduce injury incidence and thus avoid the associated long-term negative health consequences. This is especially relevant to young female athletes as they are the population at highest risk for non-contact sensorimotor error related ACL injury. This unique opportunity to enhance ACL injury prevention by targeting neural mechanisms of neuromuscular adaptation and transfer highlights the exceptional opportunity afforded by this ancillary project to the parent U01 NIH investment.